Amelioration of intrathymic T cell development and peripheral T cell reactivities in autoimmune mice undergoing therapy with a novel immunomodulator.
MRL lpr/lpr mice develop a generalized autoimmune disease associated with a massive accumulation in the peripheral lymphoid organs of abnormal, phenotypically immature T cells. Both the lymphoadenopathy and the autoimmunity are thymus-dependent and likely to arise from an aberrant pathway of intrathymic differentiation. We here present the marked beneficial effects acquired in MRL lpr/lpr mice after in vivo administration of a novel immunomodulator called linomide. The highly altered pattern of thymic subpopulations in MRL lpr/lpr mice is normalized after linomide-treatment. Concomitantly, the peripheral T cell compartment, which in MRL lpr/lpr is highly deficient in producing and responding to IL-2, gains substantial functional reactivities. We propose that linomide acts by correcting the abnormal T cell development in autoimmune MRL lpr/lpr mice. This new immunomodulator may be a useful tool for providing insight into both the pathogenesis of autoimmune disorders and intrathymic differentiation.
Spetz-Hagberg
A L
AL
Department of Immunology, University of Stockholm, Sweden.
Goldschmidt
T J
TJ
Stålhandske
T
T
Larsson-Sciard
E L
EL
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D002452:Cell Count; D002454:Cell Differentiation; D006912:Hydroxyquinolines / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D000276:Adjuvants, Immunologic; D006912:Hydroxyquinolines; C045282:roquinimex